This proposal requests support for a Keystone Symposia meeting entitled Genomic Instability and DNA Repair, organized by Junjie Chen, Karlene A. Cimprich and Michael B. Yaffe, which will be held in Keystone, Colorado from January 30 - February 4, 2011. The maintenance of genomic integrity following DNA damage depends on the coordination of DNA repair, cell cycle progression, transcriptional and post-transcriptional regulation and apoptosis. The integrity of the DNA damage response pathways plays a critical role in human health. This meeting will present the most recent advances in the field and reveal how a complex network of signaling transduction pathways are involved in DNA damage response. The overall focus of this meeting is to promote exchange of new ideas and establish collaborations among researchers involved in the field of genomic stability and DNA repair, especially related to cancer etiology and treatment. Plenary sessions cover a broad spectrum of cancer-related mechanisms of DNA damage repair processes, ranging from early detection of DNA lesions, DNA damage checkpoint control, and DNA repair to the application of this knowledge in cancer therapy.